Residential Course on Clinical Pharmacology of Antiretrovirals

2005 – 2015

Gianni Di Perri

Clinica di Malattie InfettiveUniversità degli Studi di Torino

Ospedale Amedeo di Savoia

• This project took place following the development of a Laboratory of Pharmacokinetics inside the Infectious Diseases Unit of the University of Torino

• Based on the consideration that Torino hosted the third largest italian HIV case series per single clinical center, and that antiretroviral therapy should have been administered for the entire life, we decided to devote ourselves to the study of clinical pharmacology of antiretrovirals in order to try to better understand what we were doing to our patients

• The Residential Course on Clinical Pharmacology of Antiretrovirals has grown up in parallel with our genuine enthusiasm of working in such rapidly developing field, in which most of the novelties we have seen in the last 20 years really contributed to a longer and better life for our Patients

• The Residential Course in Clinical Pharmacology of Antiretrovirals, further to be a unique opportunity for us to learn from our Speakers and Participants, it’s a sort of celebration of our happiness to have You All here, to testify how good the idea was and still is, to annually assemble those, pharmacologists, clinicians and non-clinicians, who share the same passion for this special setting

Although the acknowledgments are usually done at the end, please let me anticipate my truly sincere gratitude to two particular Friends and Collaborators Who actually made their best efforts to make this project working….

Prof. Stefano Bonora Dr. Antonio D’Avolio

..together with Mauro Sciandra…

Dr. Margherita Bracchi

…..but at the very beginning, the very first move of this project was made together with…

Dr. Marta Boffito

..Who acted as pioneer in establishing our partnership with the David Back’s Pharmacology Group in Liverpool before migrating to the Chelsea HIV Unit in London….. We are still sad but truly proud as well!

…and on this line I am also very grateful to Dr. Lorena Baietto (PhD) for Her hard work in the Lab and the efforts She has made in teaching to students, technicians and postgraduates….

Dr. Lorena Baietto

More recently we also had the privilege to work with Dr. Marco Siccardi (PhD), Who graduated with us, and after having developed remarkable technical skills and successful scientific innovation also migrated to the UK where He joined the Pharmacology Group in Liverpool.We feel sadly proud, again….

Dr. Marco Siccardi

PIsN/NtRTIsNNRTIsEIsIIs

1987 1991-2 1994 1995

AZTddIddC d4T 3TC

Pre-HAART era

1996 1997 1998 1999

SQVRTVIDV

NVPNFVDLVEFV ABV APV

HAART era

2000 2002 2003 2005 2007 2008

LPV/r TDF

T20ATVFTC

fAPV TPV DRV Fighting against Drug - R

2008 2012 2013 2014

MVC

RALRPV DTG

MVC

RALETV

Long-termmanagement

EVGCOBIbooster

Pharmacology of ARVs: The

present and the future.

Torino Jan 2005

David Back

THE UNIVERSITY

of LIVERPOOL

HIV is a disease of long-term care

AZT

ddI

ddC

d4T

3TC ABCEFV

NVP

SQV

NFV

APV

RTVIDV

LPV/r

87 88 89 95 96 97 98 99 00 01

TDF

02 03

CBV TZV

ATV

3TC QD

ddI EC

EFV 600

Little Impact UnderstandingOver optimism Long-term care

Anti-HIV Therapy Treatment History

FTC

04

NRTIs

NNRTIs

Protease

Inhibitors

05

FTC/TDF

3TC/ABC

…. courtesy of David Back, 1st Residential Course on Clinical Pharmacology of Antiretrovirals, 2005

THE UNIVERSITY

of LIVERPOOL

How to quantify the “power” or “potency” of our PK exposure?

Plasma Ctrough

n. of relevant mutationsGIQ =

Plasma Ctrough

Virtual PhenotypeVIQ =

Patient IQ

Reference IQNIQ =

[c]

Drug [c] corresponding to the EC50

90%

Concentration measured

IQ

Plasma Ctrough

IC50-90

PIQ =

Pk exposure

Viral susceptibilityIQ =

In studies on PI-experienced pts. IQ has been repeatedly found to have a higher

predictive value than drug [c] or sensitivity testing taken alone

[c] ng/mL

1 2 3 4 5 6 n. PI mutations

11000

10000

9000

8000

7000

6000

5000

4000

3000

2000

1000

Median [c]

WT MEC

R1 MEC

R2 MEC

R3 MEC

R4 MEC

R5 MEC

R6 MEC

Unusual dosing:

- Superboosting

- Increased PI dose

- Both

The Future of HIV Pharmacology: Molecule to Man

Functional

genomics

Cell lines, viral infectivity

Intracellular PK,

sanctuary sites

Clinical efficacy &

interaction studies

Phenotype

GenotypePopulations

Man

Cells and Systems

Molecule

Gene

Studies

THE UNIVERSITY

of LIVERPOOL

0

20

40

60

80

100

120

140

160

2005 2006 2007 2009 2010 2011 2012 2013 2014 2015

PARTICIPANTS TO THE COURSE, 2005-2015

INVITED SPEAKERS 2005-2015

61 speakers

28 international

9 3

1

4

3

6

1

1

Always present !

DAVID BACK

MARTA BOFFITO

SAYE KHOO

CARLO FEDERICO PERNO

SINGLE SPONSOR2005- 2009

MULTIPLE SPONSORSHIP2009 - 2015

2013

European Cup Final 2006!!

Liverpool v Fiorentina

THE UNIVERSITY

of LIVERPOOL

Stevan Jovetic was Liverpool's tormentor as he scored twice in Fiorentina's surprise win over the Reds in their Champions League Group E tie.

Page last updated at 20:35 GMT, Tuesday, 29 September 2009 21:35 UK

Fiorentina spoil Reds' swan songPublished: Thursday 10 December 2009, 0.30CETLiverpool FC 1-2 ACF FiorentinaAlberto Gilardino struck in injury time to complete a comeback win that sealed top spot for the Viola and a sorry Liverpool campaign.

Acknowledgments

THE UNIVERSITY

of LIVERPOOL

TORINO:

Stefano Bonora

Antonio D’Avolio

Mauro Sciandra

Marco Siccardi

Lorena Baietto

Cristina Tettoni

Sabrina Audagnotto

Letizia Marinaro

Jessica Cusato

Margherita Bracchi

Laura Trentini

Andrea Calcagno

Marco Simiele

Amedeo De Nicolò

Anna Lucchini

Filippo Lipani

Roberto Bertucci

Agostino Maiello

Bernardino Salassa

Francesco G. De Rosa

Chiara Montrucchio

Chiara Alcantarini

Chiara Cardellino

LIVERPOOL:

David Back

Saye Khoo

Andy Owen

Marco Siccardi

LONDON:

Marta Boffito

Margherita Bracchi

ROMA:

Andrea Antinori

Emanuele Nicastri

Giuseppe Ippolito

Alessandra Arialdo

Micol Ferrara

Alice Trentalange

Nicole Pagani

Lucio Boglione

Sarah Allegra

Debora Pensi

Pino Cariti

Paolo Bigliano

Ilaria Motta

Silvia Corcione

Maria Laura Stella

Valeria Ghisetti